Restless Legs Syndrome

Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is a long-term neurological disorder characterised by an irresistible urge to move one's legs to alleviate uncomfortable sensations. These sensations are often described as aching, tingling, or crawling, and occur primarily during periods of rest, making it difficult for sufferers to sleep. The condition is often accompanied by limb twitching during sleep, known as periodic limb movement disorder.

Signs and Symptoms

RLS symptoms vary in intensity and can range from minor annoyances to major disruptions in sleep and quality of life. The sensations typically begin or worsen during periods of inactivity, such as relaxing or trying to sleep, and are temporarily relieved by movement. Common descriptions of these sensations include "an itch you can't scratch," "buzzing," "crawling," or "limbs jerking."

Key symptoms include:

• An urge to move the limbs, usually due to uncomfortable sensations.
• Symptoms worsen during inactivity or rest.
• Temporary relief through movement.
• Symptoms are more severe in the evening or night.

These symptoms can lead to daytime sleepiness, low energy, irritability, and even depression. RLS may start at any age, including childhood, and can be progressive or intermittent.

Diagnosis

Diagnosing RLS involves a clinical evaluation based on symptoms after ruling out other possible causes. The five essential criteria for diagnosis are:

1. A strong urge to move the limbs, associated with uncomfortable sensations.
2. Symptoms start or worsen during inactivity.
3. Symptoms improve with activity.
4. Symptoms worsen in the evening or night.
5. Symptoms are not caused by other medical or behavioural conditions.

Non-essential but common indicators include a family history of RLS, a good response to dopaminergic therapy, and the presence of periodic leg movements during sleep.

Differential diagnoses include conditions such as leg cramps, arthritis, peripheral neuropathy, and drug-induced akathisia, among others.

Causes

The exact cause of RLS is unknown, but it is believed to involve changes in dopamine neurotransmission and iron metabolism in the brain. Associated conditions include iron deficiency, kidney failure, Parkinson's disease, diabetes mellitus, and pregnancy. Certain medications, such as antidepressants and antipsychotics, can also trigger or worsen RLS.

Genetics play a significant role, with more than 60% of cases being familial. Several genetic loci and genes, such as MEIS1 and BTBD9, have been associated with RLS.

Treatment

Treatment strategies for RLS include lifestyle modifications and medications. Lifestyle changes that may help reduce symptoms include improving sleep hygiene, regular exercise, and avoiding alcohol and tobacco. Stretching and walking can provide temporary relief from symptoms.

Medications

Medications used to treat RLS include:

• Dopamine agonists: Pramipexole, ropinirole, and rotigotine are effective in reducing symptoms, improving sleep quality, and enhancing quality of life. However, long-term use can lead to augmentation and other side effects.
• Gabapentinoids: Gabapentin, pregabalin, and gabapentin enacarbil are also effective and may be preferred over dopamine agonists due to lower risks of augmentation.
• Opioids: In severe or treatment-resistant cases, opioids like oxycodone and methadone may be considered, albeit with caution due to their high abuse potential and side effects.
• Iron supplementation: For individuals with low iron levels, intravenous iron supplementation can moderately improve symptoms.

Prognosis

RLS symptoms tend to worsen with age, especially in those with secondary RLS. Although there is no cure, current treatments can control symptoms, improve sleep, and enhance quality of life. Some individuals may experience remissions, but symptoms usually return over time.

Epidemiology

RLS affects approximately 2.5–15% of the American population, with women being more commonly affected than men. It is more prevalent in Caucasians and tends to increase with age. Risk factors include old age, family history, iron deficiency, pregnancy, and kidney disease. The prevalence of RLS is higher in individuals with chronic health conditions such as uraemia and end-stage kidney disease.

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Self-assessment MCQs (single best answer)

Which of the following is NOT a common description of the sensations experienced in Restless Legs Syndrome (RLS)?

Which of the following symptoms is NOT a criterion for diagnosing RLS?

Which of the following is a common non-essential indicator for diagnosing RLS?

What neurotransmitter is believed to be involved in the pathophysiology of RLS?

Which medication is NOT typically used to treat RLS?

Which of the following conditions is NOT commonly associated with RLS?

What is the prevalence range of RLS in the American population?

Which lifestyle change is NOT recommended for managing RLS symptoms?

Which of the following is a risk factor for developing RLS?

Which genetic loci or gene has been associated with RLS?